-i-
`
`Smith & Nephew Ex. 1027
`IPR Petition - USP 8,657,827
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`

`

`The declaration of the inventor
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`_X_isenclosed
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`_X_ unsigned.
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`The fee has been calculated as follows:
`
`timoOWwPp.
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`. Basic Application Fee
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`. Total Claims 74 - 20 = 54
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`. Independent Claims 9 - 3 = 6
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`. If multiple dependentclaims present, add
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`. Total Application Fee (Total of A, B, C, & D)
`
`[If small entity status is claimed,
`reduce Total Application Fee by 50%
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`. Application Fee Due(E - F)
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`a). Assignment Recording Fee of $40.00 if
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`assignment documentis enclosed
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`x $18
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`x $84
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`$280
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`=
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`=
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`$740
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`$972
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`$504
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`0
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`$2,216
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`$1,108
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`$1,108
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`$40
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`NA
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`
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`I. TOTAL FEE (G+H)
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`$1,108
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`Respectfully submitted,
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`pate:_Mau22ROODBy:
`
`DahnaS. Pasternak
`Registration No. 41,411
`
`Customer No.: 20855
`ROBINS & PASTERNAK LLP
`545 Middlefield Road, Suite 180
`Menlo Park, CA 94025
`Telephone: 650-325-7812
`Facsimile: 650-325-7823
`
`Bar Code:
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`Page 2/2
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`

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`“Express Mail" Mailing Label No. EV 081 925 454 US
`Date of Deposit 28 May 2002
`
`‘Thereby certify that this paper or fee is being deposited with the United States Postal Service "Express Mail Post
`Office to Addressee" service under 37 C.F.R. § 1.10 on the date indicated above and is addressed to the
`
`Assistant Commissioner for Patents, Washington, D.C. 20231.
`
`
`Signature of Person Mailing Paper or Fee
`
`
`
`
`Application for U.S. Letters Patent Entitled
`
`METHODS AND COMPOSITIONS FOR ARTICULAR RESURFACING
`
`claiming priority to U.S. Provisional Application
`Serial No. 60/293,488, filed May 25, 2001,
`Serial No. 60/363,527, filed March 12, 2002,
`Serial No. 60/380,695, filed May 14, 2002, and
`Serial No. Unassigned, filed May 14, 2002
`
`by Inventors:
`
`Philipp Lang
`Barry Linder
`Daniel Steines
`
`Customer No. 20855
`ROBINS & PASTERNAK LLP
`545 Middlefield Road, Suite 180
`Menlo Park, CA 94025
`Telephone: 650-325-7812
`Facsimile: 650-325-7823
`
`Attorney Docket No. 6750-0005
`
`-iii-
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`-iii-
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`6750-0005
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`METHODS AND COMPOSITIONS FOR ARTICULAR RESURFACING
`
`Cross-Reference to Related Applications
`
`This application claims the benefit of U.S. Serial Number 60/293,488 entitled
`
`“METHODS To IMPROVE CARTILAGE REPAIR SYSTEMS", filed May 25, 2001, U.S. Serial
`
`Number60/363,527, entitled "NOVEL DEVICES FoR CARTILAGE REPAIR,filed March 12,
`
`2002 and U.S. Serial Numbers 60/380,695 and Unassigned, entitled "METHODS AND
`
`COMPOSITIONS FOR CARTILAGE REPAIR," (Attorney Docket Number 6750-0005p2) and
`
`"METHODS AND COMPOSITIONSFOR JOINT REPAIR," (Attorney Docket Number 6750-
`
`0005p3), filed May 14, 2002, all of which applications are hereby incorporated by
`
`reference in their entireties.
`
`Technical Field
`
`The present invention relates to orthopedic methods, systems and prosthetic
`
`devices and moreparticularly relates to methods, systems and devices forarticular
`
`resurfacing.
`
`Background
`
`
`
`20
`
`There are various typesof cartilage, e.g., hyaline cartilage and fibrocartilage.
`
`Hyaline cartilage is found at the articular surfaces of bones, e.g., in the joints, and is
`
`responsible for providing the smooth gliding motion characteristic of moveablejoints.
`
`Articularcartilage is firmly attached to the underlying bones and measurestypically less
`
`than 5mm in thickness in human joints, with considerable variation depending on joint
`
`25
`
`and site within the joint. In addition, articular cartilage is aneural, avascular, and
`
`alymphatic. In adult humans,this cartilage derives its nutrition by a double diffusion
`
`system through the synovial membrane and through the dense matrix ofthe cartilage to
`
`reach the chondrocyte, the cells that are found in the connective tissue ofcartilage.
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`

`

`6750-0005
`
`Adult cartilage has a limited ability of repair; thus, damageto cartilage produced
`
`by disease, such as rheumatoid and/or osteoarthritis, or trauma can lead to serious
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`physical deformity and debilitation. Furthermore, as human articular cartilage ages,its
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`tensile properties change. The superficial zone of the knee articular cartilage exhibits an
`
`increase in tensile strength up to the third decadeoflife, after which it decreases
`
`markedly with age as detectable damageto type II collagen occursat the articular
`
`surface. The deep zonecartilage also exhibits a progressive decrease in tensile strength
`
`with increasing age, although collagen content does not appear to decrease. These
`
`observations indicate that there are changes in mechanical and, hence,structural
`
`organization ofcartilage with aging that, if sufficiently developed, can predispose
`
`cartilage to traumatic damage.
`
`Usually, severe damageor loss of cartilage is treated by replacementofthejoint
`
`with a prosthetic material, for example,silicone, e.g. for cosmetic repairs, or metal alloys.
`
`See, e.g., U.S. Patent No. 6,383,228, issued May 7, 2002; U.S. Patent No. 6,203,576,
`
`issued March 20, 2001; U.S. Patent No. 6,126,690, issued October 3, 2000. Implantation
`
`of prosthetic devices is usually associated with loss of underlying tissue and bone without
`
`recovery ofthe full function allowed bythe original cartilage. Serious long-term
`
`complications associated with the presence of a permanent foreign body can include
`
`infection, osteolysis and also loosening of the implant.
`
` 10
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`15
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`20
`
`Further, joint arthroplasties are highly invasive and require surgical resection of
`
`the entire or the majority of the articular surface of one or more bones. With these
`
`procedures, the marrow space is reamedin order to fit the stem of the prosthesis. The
`
`reamingresults in a loss ofthe patient’s bone stock.
`Osteolysis will frequently lead to loosening of the prosthesis. The prosthesis will
`
`25
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`subsequently have to be replaced. Since the patient’s bone stock is limited, the number of
`
`possible replacementsurgeries is also limited for joint arthroplasty. In short, over the
`
`course of 15 to 20 years, and in some casesshorter time periods, the patients may run out
`of therapeutic options resulting in a very painful, non-functionaljoint.
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`

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`6750-0005
`
`Theuse of matrices, tissue scaffolds or other carriers implanted with cells (e.g.,
`
`chrondrocytes, chondrocyte progenitors, stromal cells, mesenchymal stem cells, etc.) has
`
`also been described as a potential treatment for cartilage repair. See, also, International
`
`Publications WO; 99/51719; WO 01/91672 and WO 01/17463;U.S. Patent No. 5,283,980
`
`BI, issued September4, 2001; U.S. Patent No. 5,842,477, issued December1, 1998; U.S.
`
`Patent No. 5,769,899, issued June 23, 1998; U.S. Patent No. 4,609,551, issued Sep. 2,
`
`1986; U.S. Patent No. 5,041,138, issued Aug. 20, 199; U.S. Patent No. 5,197,985, issued
`
`March 30, 1993; U.S. Patent No. 5,226,914, issued July13, 1993; U.S. Patent No.
`
`6,328,765, issued December 11, 2001; U.S. Patent No. 6,281,195, issued August 28,
`
`2001; and U.S. Patent No. 4,846,835, issued July 11, 1989. However, clinical outcomes
`
`with biologic replacement materials such as allograft and autograft systems andtissue
`
`scaffolds have been uncertain since most of these materials cannot achieve a morphologic
`
`arrangementor structure similar to or identical to that of normal, disease-free human
`tissue. Moreover, the mechanical durability ofthese biologic replacement materialsis
`notcertain.
`
`Despite the large numberof studies in the areaof cartilage repair, the integration
`
`of the cartilage replacement material with the surrounding cartilage of the patient has
`
`proven difficult. In particular, integration can be extremely difficult due to differences in
`
`thickness and curvature between the surrounding cartilage and/or the underlying
`
`
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`20
`
`subchondral boneandthecartilage replacement material.
`
`Thus, there remains a need for methods and compositionsforjoint repair,
`
`including methods and compositionsthat facilitate the integration between the cartilage
`
`replacement system and the surroundingcartilage.
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`25
`
`Summary
`
`The present invention provides novel devices and methodsfor replacing a portion
`
`(e.g., diseased area and/or area slightly larger than the diseased area) ofa joint(e.g.,
`cartilage and/or bone) with a non-pliable, non-liquid (e.g., hard) implant material, where
`
`the implant_achieves a near anatomic fit with the surrounding structures and tissues. In
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`

`

`6750-0005
`
`cases where the devices and/or methods include an element associated with the
`
`underlying articular bone, the invention also provides that the bone-associated
`
`element achieves a near anatomic alignment with the subchondral bone. The invention
`
`also provides for the preparation of an implantation site a single cut.
`
`In one aspect, the invention includes a method for providing articular replacement
`
`material, the method comprising the step of producing articular replacement(e.g.,
`
`cartilage replacement material) of selected dimensions(e.g., size, thickness and/or
`
`curvature).
`
`
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`20
`
`In another aspect, the invention includes a method of makingcartilage repair
`material, the method comprising the steps of (a) measuring the dimensions(e.g.,
`
`thickness, curvature and/or size) of the intended implantationsite or the dimensions of
`
`the area surrounding the intended implantation site; and (b) providing cartilage
`
`replacement material that conformsto the measurements obtained in step (a). In certain
`aspects, step (b) comprises measuring the thickness ofthe cartilage surrounding the
`intended implantation site and measuring the curvature of the cartilage surrounding the
`intended implantationsite. In other embodiments, step (a) comprises measuringthe size
`of the intended implantation site and measuring the curvature ofthe cartilage surrounding
`the intended implantation site. In other embodiments, step (a) comprises measuring the
`thickness of the cartilage surrounding the intended implantation site, measuring the size
`of the intended implantation site, and measuring the curvatureofthe cartilage
`
`surrounding the intended implantationsite.
`
`In any of the methods described herein, or more componentsofthe articular
`
`25
`
`replacement material(e.g., the cartilage replacement material) is non-pliable, non-liquid,
`solid or hard. The dimensions of the replacement material may be selected following
`intraoperative measurements, for example measurements made using imaging techniques
`such as ultrasound, MRI, CT scan, x-ray imaging obtained with x-ray dye and
`fluoroscopic imaging. A mechanical probe (with or without imaging capabilities) may
`also be used to selected dimensions, for example an ultrasoundprobe,a laser, an optical
`probe and a deformable material.
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`

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`6750-0005
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`In any of the methods described herein, the replacement material may be selected
`(for example, from a pre-existing library of repair systems), grown from cells and/or
`hardened from various materials. Thus, the material can be producedpre- or post-
`operatively. Furthermore, in any of the methods described herein the repair material may
`also be shaped(e.g., manually, automatically or by machine), for example using
`mechanicalabrasion,laser ablation, radiofrequency ablation, cryoablation and/or
`
`enzymatic digestion.
`
`In any of the methods described herein,the articular replacement material may
`comprise synthetic materials (e.g., metals, polymers, alloys or combinationsthereof) or
`biological materials such as stem cells, fetal cells or chondrocytecells.
`
`In anotheraspect, the invention includes a method of repairing a cartilage in a
`subject, the method of comprising the step of implantating cartilage repair material
`prepared according to any of the methods described herein.
`
`In yet another aspect, the invention provides a method of determining the
`curvature of an articular surface, the method comprising the step of(a) intraoperatively
`measuring the curvatureof the articular surface using a mechanical probe. The articular
`surface may comprise cartilage and/or subchondral bone. The mechanical probe (with or
`without imaging capabilities) may include, for example an ultrasoundprobe,a laser, an
`optical probe and/or a deformable material.
`
`In a still further aspect, the invention provides a method of producingan articular
`replacement material comprising the step of providing an articular replacement material
`that conformsto the measurements obtained by any of the methods of describedherein.
`
`Ina still further aspect, the invention includesa partial articular prosthesis
`comprising a first component comprising a cartilage replacement material; and a second
`component comprising one or more metals, wherein said second componenthas a
`curvature similar to subchondral bone, wherein said prosthesis comprises less than about
`80% ofthe articular surface. In certain embodiments, the first and/or second component
`comprises a non-pliable material (e.g., a metal, a polymer, a metal allow,a solid
`biological material), Other materials that may be includedin the first and/or second
`
` 10
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`20
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`25
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`

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`6750-0005
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`components include polymers, biological materials, metals, metal alloys or combinations
`
`thereof. Furthermore, one or both components may be smooth or porous(or porous
`
`coated). In certain embodiments,the first component exhibits biomechanical properties
`
`(e.g., elasticity, resistance to axial loading or shear forces) similarto articular cartilage.
`
`Thefirst and/or second component can be bioresorbable and, in addition,the first or
`
`second components may be adapted to receive injections.
`
`In another aspect, a partial articular prosthesis comprising an external surface
`
`located in the load bearing area of an articular surface, wherein the dimensions ofsaid
`
`external surface achieve a near anatomic fit with the adjacent cartilage is provided. The
`
`prosthesis of may further comprise one or more metals or metal alloys.
`
`In yet anotheraspect, an articular repair system comprising (a) cartilage
`
`replacement material, wherein said cartilage replacement material has a curvature similar
`
`to surrounding or adjacentcartilage; and (b) at least one non-biologic material, wherein
`
`said articular surface repair system comprises a portion ofthe articular surface equal to or
`
`smaller than the weight-bearing surface is provided. In certain embodiments, the
`
`cartilage replacement material is non-pliable (e.g., hard hydroxyapatite, etc.). In certain
`
`embodiments, the system exhibits biomechanical (e.g., elasticity, resistance to axial
`
`loading or shear forces) and/or biochemical properties similar to articular cartilage. The
`
`first and/or second component can be bioresorbable and, in addition, the first or second
`
`
`
`20
`
`components may be adapted to receive injections.
`
`Inastill further aspect of the invention, an articular surface repair system
`
`comprising a first component comprising a cartilage replacement material, wherein said
`
`first component has dimensionssimilar to that of adjacent or surroundingcartilage; and a
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`second component, wherein said second componenthas a curvature similar to
`
`25
`
`subchondral bone, wherein said articular surface repair system comprises less than about
`
`80% ofthe articular surface (e.g., a single femoral condyle,tibia, etc.) is provided. In
`
`certain embodiments, the first component is non-pliable (e.g., hard hydroxyapatite, etc.).
`
`In certain embodiments, the system exhibits biomechanical (e.g., elasticity, resistance to
`
`axial loading or shear forces) and/or biochemical properties similar to articular cartilage.
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`

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`6750-0005
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`The first and/or second component can be bioresorbable and, in addition, the first or
`
`second components may be adaptedto receive injections. In certain embodiments, the
`
`first componenthas a curvature and thicknesssimilar to that of adjacent or surrounding
`cartilage. The thickness and/or curvature may vary across the implant material.
`
`In a still further embodiment, a partial articular prosthesis comprising(a) a metal
`
`or metalalloy; and (b) an external surface located in the load bearing area of an articular
`
`surface, wherein the external surface designed to achieve a near anatomic fit with the
`
`adjacent cartilage is provided.
`
`Anyofthe repair systems or prostheses described herein(e.g., the external
`
`surface) may comprise a polymeric material, for example attached to said metal or metal
`
`alloy. Further, any of the systems or prostheses described herein can be adapted to
`
`receive injections, for example, through an opening in the external surface of said
`
`cartilage replacement material (e.g., an opening in the external surface terminates in a
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`plurality of openings on the bone surface). Bone cement, therapeutics, and/or other
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`bioactive substances may be injected through the opening(s). In certain embodiments,
`bone cementis injected under pressure in order to achieve permeation ofportions of the
`
`marrow space with bone cement.
`
`These and other embodiments of the subject invention will readily occur to those
`
`of skill in theart in light of the disclosure herein.
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`
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`20
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`Brief Description of the Figures
`
`The file of this patent contains at least one drawing executed in color. Copies of
`this patent with color drawing(s) will be provided by the Patent and Trademark Office
`
`upon request and paymentof the necessary fee.
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`25
`
`FIG.1 is a flowchart depicting various methods of the present invention
`including, measuring the size of an area of diseasedcartilage or cartilage loss, measuring
`the thickness of the adjacent cartilage, and measuring the curvatureof the articular
`
`surface and/or subchondral bone. Based onthis information,a best fitting implant can be
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`

`

`6750-0005
`
`selected from a library of implants or a patient specific custom implant can be generated.
`
`The implantation site is subsequently prepared and the implantation is performed.
`
`FIG.2 is a color reproduction of a three-dimensional thickness map ofthe
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`articular cartilage of the distal femur. Three-dimensional thickness maps can be
`
`generated, for example, from ultrasound, CT or MRI data. Dark holes within the
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`substances ofthe cartilage indicate areas of full thickness cartilage loss.
`
`FIG. 3 shows an example of a Placido disc of concentrically arranged circles of
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`light.
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`10
`
`
`
` al
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`FIG. 4 shows an example of a projected Placido disc on a surface of fixed
`
`curvature.
`
`FIG. 5 shows an example of a 2D color-coded topographical map of an
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`irregularly curved surface.
`
`FIG.6 shows an example of a 3D color-coded topographical map of an
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`irregularly curved surface.
`
`FIG.7 showsa reflection resulting from a projection of concentriccircles oflight
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`(Placido Disk) on each femoral condyle, demonstrating the effect of variation in surface
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`contour on the reflected circles.
`
`FIG. 8A-H are schematics of various stages of knee resurfacing. FIG. 8A shows
`
`an example of normalthicknesscartilage in the anterior, central and posterior portion of a
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`20
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`femoral condyle 800 and a cartilage defect 805 in the posterior portion of the femoral
`
`condyle. FIG. 8B showsan imaging technique or a mechanical, optical, laser or
`
`ultrasound device measuring the thickness and detecting a sudden changein thickness
`
`indicating the margins of a cartilage defect 810. FIG. 8C shows a weight-bearing surface
`
`815 mapped onto the articular cartilage. Cartilage defect 805 is located within the weight-
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`25
`
`bearing surface 815. FIG. 8D showsan intended implantation site (stippled line) 820 and
`
`cartilage defect 805. The implantation site 820 is slightly larger than the area of diseased
`
`cartilage 805. FIG. 8E depicts placement of a single componentarticular surface repair
`
`system 825. The external surface ofthe articular surface repair system 826 has a
`
`curvature similar to that of the surrounding cartilage 800 resulting in good postoperative
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`

`6750-0005
`
`alignment between the surrounding normalcartilage 800 and the articular surface repair
`system 825. FIG. 8F shows an exemplary multi-componentarticular surface repair
`
`system 830. The distal surface of the deep component $32 has a curvature similar to that
`
`of the adjacent subchondral bone 835. The external surface ofthe superficial component
`
`837 has a thickness and curvature similar to that of the surrounding normalcartilage 800.
`FIG. 8G shows an exemplary single component articular surface repair system 840 with
`
`a peripheral margin 845 substantially non-perpendicular to the surrounding or adjacent
`normalcartilage 800. FIG. 8H showsan exemplary multi-componentarticular surface
`
`repair system 850 with a peripheral margin 845 substantially non-perpendicular to the
`
`surrounding or adjacent normalcartilage 800.
`
`FIG.9, A through E, are schematics depicting exemplary knee imaging and
`
`resurfacing. FIG. 9A is a schematic depicting a magnified view ofan area of diseased
`
`cartilage 905 demonstrating decreased cartilage thickness when compared to the
`
`surrounding normalcartilage 900. The margins 910 of the defect have been determined.
`
`FIG.9B is a schematic depicting measurementofcartilage thickness 915 adjacentto the
`
`defect 905. FIG. 9C is a schematic depicting placement of a multi-component mini-
`
`prosthesis 915 for articular resurfacing. The thickness 920of the superficial component
`923 closely approximates that of the adjacent normalcartilage 900 andvaries in different
`regionsof the prosthesis. The curvature of the distal portion of the deep component925is
`similar to that of the adjacent subchondral bone 930. FIG.9D is a schematic depicting
`placement of a single component mini-prosthesis 940 utilizing fixturing stems 945. FIG.
`9E depicts placement of a single component mini-prosthesis 940 utilizing fixturing stems
`945 and an opening 950 for injection of bone cement 955. The mini-prosthesis has an
`opening at the external surface 950 for injecting bone cement 955orother liquids. The
`bone cement 955 can freely extravasate into the adjacent bone and marrow space from
`several openings at the undersurface of the mini-prosthesis 960 thereby anchoring the
`mini-prosthesis.
`
`FIG. 10Ato C, are schematics depicting other exemplary knee resurfacing
`devices and methods. FIG 10A is a schematic depicting normal thickness cartilage in the
`
`
`
`20
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`25
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`

`

`6750-0005
`
`anterior and central and posterior portion of a femoral condyle 1000 and a large area of
`
`diseased cartilage 1005 in the posterior portion of the femoral condyle. FIG. 10B depicts
`
`placement of a single componentarticular surface repair system 1010. The implantation
`
`site has been prepared with a single cut. The articular surface repair system is not
`
`5
`
`perpendicular to the adjacent normalcartilage 1000. FIG. 10C depicts a multi-
`
`componentarticular surface repair system 1020. The implantation site has been prepared
`
`with a single cut. The deep component 1030 has a curvature similar to that of the adjacent
`
`subchondral bone 1035. The superficial component 1040 has a curvature similar to that of
`
`the adjacentcartilage 1000.
`
`10
`
`FIG. 11A and B show exemplary single and multiple component devices. FIG
`
`11A showsan exemplary a single componentarticular surface repair system 1100 with
`
`varying curvature andradii. In this case, the articular surface repair system is chosen to
`
`
` concaveportions.
`
`include convex and concaveportions. Such devices can be preferable in a lateral femoral
`
`condyle or small joints such as the elbow joint. FIG. 11B depicts a multi-component
`
`15
`
`articular surface repair system with a deep component 1110 that mirrors the shape of the
`
`subchondral bone and a superficial component 1105 closely matching the shape and
`
`curvature of the surrounding normalcartilage 1115. The deep component 1110 and the
`
`superficial component 1105 demonstrate varying curvatures and radii with convex and
`
`20
`
`Detailed Description of the Invention
`
`The current invention provides for methods and devices for integration of
`
`cartilage replacement or regenerating materials.
`
`Before describing the present invention in detail, it is to be understoodthatthis
`
`25.
`
`mvention is not limited to particular formulations or process parameters as such may, of
`
`course, vary. It is also to be understood that the terminology used hereinis for the
`
`purpose of describing particular embodimentsof the invention only, and is not intended
`
`to be limiting.
`
`10
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`

`

`6750-0005
`
`The practice of the present invention employs, unless otherwise indicated,
`
`conventional methods of x-ray imaging and processing, x-ray tomosynthesis, ultrasound
`
`including A-scan, B-scan and C-scan, computed tomography (CT scan), magnetic
`
`resonance imaging (MRI), optical coherence tomography, single photon emission
`
`tomography (SPECT)and positron emission tomography (PET) within the skill of the art.
`
`Such techniques are explained fully in theliterature. See, e.g., X-Ray Structure
`
`Determination: A Practical Guide, 2nd Edition, editors Stout and Jensen, 1989, John
`
`Wiley & Sons, publisher; Body CT: A Practical Approach, editor Slone, 1999, McGraw-
`
`Hill publisher; X-ray Diagnosis: A Physician's Approach, editor Lam, 1998 Springer-
`
`10
`
`Verlag, publisher; and Dental Radiology: Understanding the X-Ray Image, editor Laetitia
`
`Brocklebank 1997, Oxford University Press publisher.
`
`All publications, patents and patent applications cited herein, whether above or
`
`below,are hereby incorporated by referencein their entirety.
`
`It must be noted that, as used in this specification and the appended claims, the
`
`15
`
`singular forms “a”, “an”, and “the” includepluralreferences unless the content clearly
`
`dictates otherwise. Thus, for example, reference to “an implantation site” includes a one
`
`or more suchsites.
`
`Definitions
`
`20
`
`Unless defined otherwise, all technical and scientific terms used herein have the
`
`same meaning as commonly understood by one of ordinary skill in the art to which the
`
`invention pertains. Although any methods and materials similar or equivalent to those
`
`described herein can be used in the practice for testing of the present invention, the
`
`preferred materials and methodsare described herein.
`
`25
`
`The term "arthritis" refers to a group of conditions characterized by progressive
`
`deterioration ofjoints. Thus, the term encompassesa group ofdifferent diseases
`
`including,but not limited to, osteoarthritis (OA), rheumatoidarthritis, seronegative
`
`spondyloarthropathies and posttraumatic joint deformity.
`
`
`
`
`11
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`

`

`6750-0005
`
`The term "articular" refers to any joint. Thus, "articular cartilage" refers to
`
`cartilage in a joint such as a knee, ankle, hip, etc. The term "articular surface" refers to a
`
`surface of an articulating bone that is covered by cartilage. For example, in a knee joint
`
`several different articular surfaces are present,e.g. in the patella, the medial femoral
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`condyle, the lateral femoral condyle, the medialtibial plateau and the lateral tibial
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`plateau.
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`The term “weight-bearing surface”refers to the contact area between two
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`opposingarticular surfaces during activities of normaldaily living.
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`The term "cartilage" or "cartilage tissue" as used herein is generally recognized in
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`the art, and refers to a specialized type of dense connective tissue comprising cells
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`embedded in an extracellular matrix (ECM)(see, for example, Cormack, 1987, Ham's
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`Histology, 9th Ed., J. B. Lippincott Co., pp. 266-272). The biochemical composition of
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`cartilage differs according to type Several types of cartilage are recognizedin theart,
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`including, for example, hyaline cartilage such as that found within the joints, fibrous
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`cartilage such as that found within the meniscus and costal regions, and elastic cartilage.
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`Hyaline cartilage, for example, comprises chondrocytes surrounded by a dense ECM
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`consisting of collagen, proteoglycans and water. Fibrocartilage can form in areas of
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`hyaline cartilage, for example after an injury or, more typically, after certain types of
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`surgery. The production of any type ofcartilage is intended to fall within the scope ofthe
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`invention.
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`Furthermore, although described primarily in relation to methodsfor use in
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`humans, the invention mayalso be practiced so as repaircartilage tissue in any mammal
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`in need thereof, including horses, dogs, cats, sheep, pigs, among others. The treatment of
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`such animals is intendedto fall within the scope of the invention.
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`The terms “articular repair system" and "articular surface repair system" include
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`any system (including, for example, compositions, devices and techniques) to repair, to
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`replace or to regenerate a portion of a joint or an entire joint. The term encompasses
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`systems that repair articular cartilage, articular bone or both boneandcartilage. Articular
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`surface repair systems may also include a meniscal repair system (e.g., meniscal repair
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`system can be composedofa biologic or non-biologic material), for example a meniscal
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`repair system having biomechanical and/or biochemical properties similar to that of
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`healthy menisci. See, for example, U.S. Patent Publication No. US 2002/00228841A1.
`The meniscal repair system can be surgically or arthroscopically attachedto the joint
`capsule or one or more ligaments. Non-limiting examples of repair systems include
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`autologous chondrocyte transplantation, osteochondral allografting, osteochondral
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`autografting, tibial corticotomy, femoral and/ortibial osteotomy. Repair systems also
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`include treatment with cartilage or bone tissue grown ex vivo, stem cells, cartilage
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`material grown with use of stem cells, fetal cells or immature or mature cartilage cells, an
`artificial non-human material, an agent that stimulates repair of diseased cartilagetissue,
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`an agent that stimulates growth of cells, an agent that protects diseased cartilage tissue
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`and that protects adjacent normalcartilage tissue. Articular repair systems include also
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`treatment with a cartilage tissue transplant, a cartilage tissue graft, a cartilage tissue
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`implant, a cartilage tissue scaffold, or any other cartilage tissue replacement or
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`regenerating material. Articular repair systems include also surgicaltools that facilitate
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`the surgical procedure required for articular repair, for example tools that prepare the area
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`of diseased cartilage tissue and/or subchondral bonefor receiving, for example, a
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`cartilage tissue replacement or regenerating material. The term "non-pliable" refers to
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`material that cannot be significantly bent but mayretain elasticity.
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`The terms "replacement material" or "regenerating material" include a broad
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`range of natural and/or synthetic materials used in the methods described herein, for
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`example, cartilage or bone tissue grown ex vivo, stem cells, cartilage material grown from
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`stem cells, stem cells, fetal cell, immature or mature cartilage cells, an agent that
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`stimulates growthofcells, an artificial non-human material, a cartilage tissue transplant,
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`a cartilage tissue graft, a cartilage tissue implant, a cartilage tissue scaffold, or a cartilage
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`tissue regenerating material. The term includes biological materials isolated from various
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`sources (e.g., cells) as well as modified (e.g., genetically modified) materials and/or
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`combinations of isolated and modified materials.
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`The term "imagingtest" includes, butis not limited to, x-ray based techniques
`(such as conventional film basedx-ray films, digital x-ray images, single and dual x-ray
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`absorptiometry, radiographic absorptiometry); digital x-ray tomosynthesis, x-ray imaging
`including digital x-ray tomosynthesis with use of x-ray contrast agents, for example after
`intra-articular injection, ultrasound including broadbandultrasound attenuation
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`measurement and speed of sound measurements, A-scan, B-scan and C-scan; computed
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`tomography; nuclear scintigraphy; SPECT;positron emission tomography, optical
`coherence tomography and MRI. Oneor more of these imaging tests may be used in the
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`methods described herein, for example in order to obtain certain morphological
`information about oneorseveral tissues such as bone including bone mineral density and
`curvature of the subchondral bone, cartilage including biochemical composition of
`cartilage, cartilage thickness, cartilage volume, cartilage curvature, size of an area of
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`diseased cartilage, severity of cartilage disease or cartilage loss, marrow including
`marrow composition, synovium including synovial inflammation, lean andfatty tissue,
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`and thickness, dimensions and volumeof soft and hard tissues. The imaging test can be
`performed with use of a contrast agent, such as Gd-DTPAin the case of MRI.
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`The term “A — scan”refers to an ultrasonic technique where an ultrasonic source
`transmits an ultrasonic waveinto an object, such as patient's body, and the amplitude of
`the returning echoes(signals) are recorded as a function of time. Only structures thatlie
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`along the direction ofpropagation are interrogated. As echoes return from interfaces
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`within the object ortissue, the transducer crystal produces a voltagethat is proportional
`to the echo intensity. The sequenceofsignal acquisition and processing of the A - scan
`